Randomized Pharmacokinetic Study of a Highly Purified Human Chorionic Gonadotropin and of a Recombinant Human Chorionic Gonadotropin Following Single Subcutaneous Administration in Healthy Women

摘要

Background and Objectives Exogenous human chorionic gonadotropin (hCG) acts on the final phase of the follicle maturation. Choriomon(R), a highly purified hCG formulation, is approved in many European and extra-European countries for the induction of ovulation after stimulation of follicular development. The present study compares hCG bioavailability of Choriomon(R) (Test product) versus a recombinant hCG preparation (Ovitrelle(R); Reference product). Methods In this randomized, two-way cross-over study, 26 healthy women received a single dose of Choriomon(R) (10,000 IU) and Ovitrelle(R) (250 mu g; 6500 IU) by subcutaneous injection. hCG was determined in serum up to 192 h post-dose. Dose-normalized peak concentration (C-max) and area under the concentration-time curve up to the time of the last quantifiable concentration (AUC(0-t)) and extrapolated to infinity (AUC(0-infinity)) were calculated and compared between the two treatments. Results Serum hCG concentrations increased rapidly with a very similar pharmacokinetic curve for the two products. The test/reference geometric means ratio (GMR) for AUC(0-t) and AUC(0-infinity) corresponded to 121.31 and 119.81, and the upper limits of the 90 confidence intervals (CIs) (130.21 and 128.51, for AUC(0-t) and AUC(0-infinity), respectively) exceeded the 125 bioequivalence threshold. C-max GMR was 146.89, indicating a rate of hCG absorption approximately 50 greater for the test product (90 CI 132.30-163.10). Half-life (t(1/2)) was very similar (36.77 +/- 5.11 h and 38.63 +/- 6.08 h), whereas time to achieve C-max (t(max)) significantly differed, with median values of 16 h and 24 h for Choriomon(R) and Ovitrelle(R), respectively, (p = 0.0023). Conclusions The differences between Choriomon(R) and Ovitrelle(R) pharmacokinetic parameters can be ascribed to the different raw source of the products and are reflected in the approved dose regimens of the two hCG formulations. The observed lack of bioequivalence between the two compounds at the given doses is not clinically relevant, as results from Phase III studies indicated similar clinical efficacy and safety. The safety data are in line with the known safety profile of the two products. Clinicaltrials.gov registration no NCT03735030.